Mycobacteria-induced autoantibody production is associated with susceptibility to infection but not with host propensity to develop autoimmune disease

Abstract

SUMMARYMycobacteria cause increase in autoantibody production in the host during the first weeks of infection. The level of the autoantibody enhancement varies widely in different hosts, suggesting that it depends on features of the host make-up. We have investigated the participation of two characteristics of the host in the modulation of mycobacteria-induced autoantibody production: (i) the host being genetically determined to later develop spontaneous autoimmune disease; (ii) the host being susceptible/resistant to mycobacterial infection. Mycobacterium avium infection was studied in 3-month-old mice that are prone (NZB and C57Bl/6-lpr/lpr strains) or not (NZW and C.D2 strains) to develop, when older, autoimmune disease; these murine strains are either naturally susceptible (C57Bl/6-lpr/lpr and NZW) or resistant (NZB and C.D2) to mycobacteria. Mycobacterium avium infection was produced by i.p. injection of 3 x 107 viable bacilli. At days 15 and 30 of the infection, we determined the following parameters: (i) number of cells producing natural autoantibodies (splenic cells showing surface antibodies against bromelain-treated mouse (BrM) erythrocytes); (ii) suppression of the primary response to T cell-dependent antigen (i.e. to sheep erythrocytes); (iii) immunoglobulin classes and IgG isotypes; (iv) titres of anti-dsDNA antibodies; and (v) serum concentrations of interferon-gamma (IFN--y). We found that the highest elevations in natural autoantibodies were associated with hosts being naturally susceptible to mycobacteria, but not with the host being genetically determined to later develop autoimmune disease. The rise in autoantibodies was predominantly of the IgM type, being associated with suppression of the T cell response and accompanied by increase in serum IFN-y. Mycobacteria failed to induce any significant enhancement in pathogenic anti-dsDNA antibodies. Our data suggest that the finding of a high level of autoantibodies during the early phase of mycobacterial infection reflects host susceptibility to the infectious agent, and that it is not related with its propensity to later develop autoimmune disorders.

Analysis of a wild mouse promoter variant reveals a novel role for FcγRIIb in the control of the germinal center and autoimmunity

“…Control of the GC reaction has long been proposed to constitute a crucial checkpoint preventing the breakdown of immune tolerance ( Goodnow et al, 2005 ). As total GC B cells, but not those specific for NP, were increased in FcγRIIb wild/H1 KI mice, we wondered whether immunization might lead to the bystander activation of autoreactive clones in these mice, a phenomenon observed after viral or bacterial infection in humans and mice ( Zinkernagel et al, 1990 ; Brás and Aguas, 1995 ; Hunziker et al, 2003 ). 8 d after NP-KLH immunization, higher titers of antichromatin and anti–double-stranded DNA (dsDNA) IgM and IgG1 were observed in FcγRIIb wild/H1 KI mice.…”